The Novel Platinum Analog Dicycloplatin Provides Reliable Growth Inhibition of Urothelial Carcinoma Cells In Vitro.

BACKGROUND/AIM: Platinum-based chemotherapies are a component of standard-of-care regimens for urothelial carcinoma (UC). These nephrotoxic drugs are often dose-limiting, with cisplatin and carboplatin being the most commonly used. Dicycloplatin (DCP) has better solubility and stability, with comparable efficacy and better tolerability. Some suggest the use of DCP as primary treatment for non-muscle-invasive bladder cancer. We exposed UC cell lines to DCP in vitro to assess its efficacy. MATERIALS AND METHODS: A high grade (IV) in vitro UC cell line (TCCSUP) was exposed to varying concentrations of cisplatin (0-600 µg/ml), carboplatin (0-600 µg/ml), oxaliplatin (0-4.0 µg/ml), and DCP (0-350 µg/ml). Grade II-IV cells were exposed to varying concentrations of DCP (0-350 µg/ml) to assess time- and concentration-dependent growth inhibition, and simulate intravesical treatment. Growth inhibition was determined following 24, 48, and 72 h of exposure, using a tetrazolium dye to assess mitochondrial dehydrogenase activity. RESULTS: DCP, cisplatin, and carboplatin effectively achieved >90% cell kill at 72 h. Concentrations of 325 µg/ml DCP, 50 µg/ml cisplatin, and 600 µg/ml carboplatin were sufficient for >90% cell-kill, with cisplatin demonstrating the highest efficacy at the lowest concentration/time intervals. Dose- and time-dependent cell kill were demonstrated at varying concentrations of DCP in grade II-IV cell lines, including cells exposed intravesically. CONCLUSION: In vitro, DCP demonstrates cell-killing efficacy in a time- and concentration-dependent manner in grade II-IV UC cell lines, showing promise for its intravenous, oral, and intravesical use for bladder UC in both primary and adjuvant/neoadjuvant settings.

First American Cancer Patient to Receive Dicycloplatin (DCP) Chemotherapy Achieves Remission After Seven Weeks of DCP Capsules - A Case Report.

BACKGROUND: The majority of bladder cancer patients experience recurrence. Cisplatin is the standard chemotherapy for muscle-invasive bladder cancer though adverse effects are often severe. CASE REPORT: Intravenous (IV) dicycloplatin (DCP) sustained remission in an American bladder cancer patient for five years. A recurrent mass was observed in July 2021. The patient received DCP capsules for seven weeks with no significant side-effects. Complete blood count with differential and a basic metabolic panel showed no adverse effects of DCP capsules on the bone marrow, liver or renal parameters. Cystoscopy after oral DCP found no evident bladder tumors; cytology was negative for high-grade urothelial carcinoma. CONCLUSION: In this patient, DCP-capsules appeared to be as effective as DCP-IV for achieving bladder cancer remission. Both forms of DCP chemotherapy are convenient, active against several cancer types, with decreased adverse effects compared to cisplatin. Both have been available for treating cancer patients in China. A USA clinical trial of DCP in bladder and other cancers appears warranted.

Utilizing trans-scrotal percutaneous cystolitholapaxy in the case of massive inguinoscrotal herniation of the bladder with concomitant bladder calculi.

BACKGROUND: Massive herniation of the bladder presents a rare diagnostic challenge. Rarely, bladder herniation is complicated by the development of bladder calculi. We present a therapeutic approach for this situation. CASE PRESENTATION: A 90-year-old presented with recurrent urinary tract infections secondary to bladder calculi in the setting of inguinoscrotal bladder herniation. He subsequently underwent successful trans-scrotal percutaneous cystolitholapaxy as a creative approach to an unusual presentation. CONCLUSION: Massive inguinoscrotal herniation of the bladder is a rare clinical entity with significant morbidity and mortality. Intervention requires a balance of patient health status and anatomy, lending to creative approaches as necessary.

Perirenal extra-adrenal myelolipoma.

Myelolipomas are rare tumors consisting of both adipose and hematopoietic tissue and are typically found within the adrenal gland. Extra-adrenal involvement is rare, especially those tumors involving the perirenal space and collecting system. We report a case of a patient with an incidentally discovered perirenal mass that was initially concerning for a retroperitoneal liposarcoma. Following surgical resection and pathological analysis, the lesion was found to be an extra-adrenal myelolipoma. This case report and review of the literature demonstrates the importance of the proper work-up and management of perirenal lipoma variants while addressing the issues of tissue biopsy, surgical intervention, and pre- and post-operative surveillance.

In vitro regulation of cell growth and angiogenesis by inositol hexaphosphate in bladder cancer.

BACKGROUND: Inositol Hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is found in food sources high in fiber content. We hypothesized that IP6 would inhibit the cell growth rate of bladder cancer in vitro. METHODS: T24 and TCCSUP bladder cancer cell lines were treated with titrating doses of IP6 (0.3, 0.6 and 0.9 mM/well). Cell viability and vascular endothelial growth factor levels were measured. RESULTS: Significant reductions (p < 0.001) in cellular growth were noted in both cell lines at all doses and time points tested, with the exception of 0.3 mM IP6 at 24 hours in the T24 cell line. The percent inhibition of vascular endothelial growth factor was significantly higher than that observed in the TCCSUP cell line at 48 and 72 hours with 0.3 mM IP6 (p < 0.001). The T24 cells exhibited the same level of inhibition at 24 and 48 hours with 0.6 mM dose of IP6 and at 72 hours with the 0.3 mM dose (p < 0.001). CONCLUSIONS: In vitro treatment of bladder cancer with the common dietary polyphosphorylated carbohydrate IP6 significantly decreased cellular growth by anti-angiogenic mechanisms. We feel that this data warrants further investigation and consideration for initiation of clinical trials to evaluate the safety and clinical utility of this agent.

Testicular trauma resulting in spermatic vessel thrombosis and testicular loss: a case report.

Testicular ischemia is typically seen with cases of testicular torsion. Twisting of the spermatic cord and compromise of testicular blood supply can induce testicular loss if not promptly discovered and treated. Non-torsion causes of testicular ischemia are uncommon with rare citations in the literature. Herein, we present a case of testicular ischemia induced by traumatic thrombosis of the spermatic vessels.

Traumatic complete urethral disruption: the West Virginia experience.

Type III complete urethral disruption is an uncommon injury that occurs primarily in male patients with pelvic trauma. Herein we present our results from management of this condition. Management should initially be conservative with a catheter placement in all cases. Full return of urinary function was noted in all patients managed endoscopically, and in 1 of 3 of patients managed with open urethroplasty. Erectile function was preserved in 2 of 3 of patients managed with endoscopic repair, and in none of the patients managed with open urethroplasty. The most common surgical urologic complication was traumatic urethral stricture.

Asymptomatic advanced pediatric papillary renal cell carcinoma presenting as a pulmonary embolus.

Renal cell carcinoma in the pediatric population is a rare disease. A limited number of cases of renal cell carcinoma exist worldwide in the pediatric population. Reported herein is a case of a 17-year-old female who presented to an outside hospital with gross hematuria and shortness of breath. She was found to have a pulmonary embolus on computed tomography scan. After further imaging, a large renal mass with renal vein and vena cava involvement was observed. Intraoperatively, the tumor demonstrated extensive invasion of the wall of the vena cava.

Leiomyoma of the urinary bladder presenting as urinary retention in the female.

A case of leiomyoma of the urinary bladder, a rare benign tumor, in a 56-year-old female first seen with bilateral flank pain radiating to both groins, is reported. Examination showed a well developed female with obesity (260 pounds) and elevated blood pressure (132/90 mmHg). Evaluation with ultrasound, cystoscopy, urodynamics, and cytology contributed to the diagnosis of urinary bladder leiomyoma. Ultrasound detected a mass in the urinary bladder, and it was confirmed by cystoscopy to be a 5 cm to 6 cm bladder mass on the anterior bladder wall. The mass was prolapsing as a ball valve into the urethra at the level of the bladder neck. Frozen section of the mass showed it to be leiomyoma.

Sexual dysfunction in patients with painful bladder syndrome.

PURPOSE: The degree of sexual dysfunction in patients with Painful Bladder Syndrome (PBS) has not been documented previously. The Female Sexual Function Index (FSFI) was used to measure the degree of female sexual dysfunction (FSD) in these patients. MATERIALS AND METHODS: The FSFI was administered on-line to female patients with self-reported PBS. This 19-item questionnaire evaluated FSD in six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain. RESULTS: The data was analyzed on an item-for-item basis and by the six domains of sexual dysfunction for 100 patients and compared to a control group of 131 healthy volunteers and a second group consisting of 128 patients with Female Sexual Arousal Disorder (FSAD). When compared with the controls, PBS patients self-report sexual dysfunction in all domains evaluated by the FSFI. CONCLUSIONS: The degree of FSD in PBS patients is significantly higher in all domains when compared to the control group.

Sexual dysfunction in patients with painful bladder syndrome is age related and progressive.

INTRODUCTION/OBJECTIVE: The degree of sexual dysfunction in patients with painful bladder syndrome (PBS) across their lifespan has not been previously documented. MATERIAL AND METHODS: The Female Sexual Function Index (FSFI) is a research tool to measure the degree of clinical female sexual dysfunction (FSD). This 19-item questionnaire evaluates FSD in six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain. This study used the FSFI with the additional variables of age, geographical location, and current medications. The participants were not blinded to the fact that this study was examining the link between PBS and FSD. Each question in the survey was targeted to a specific variable of FSD and the answers were rated on a Lickert scale. RESULTS: When compared with controls, PBS patients self-report significant sexual dysfunction in all domains evaluated by the FSFI (p < 0.001). Age-specific results were observed in regards to the domains of arousal, lubrication, and pain (p < 0.01). CONCLUSIONS: PBS patients report significant FSD in all domains when compared to controls (p < 0.001). Significant differences in the domains of arousal, lubrication, and pain exist between respondents < 30 years old and in those > 50 years of age. The extent of sexual dysfunction is worse in the areas of pain in each age group evaluated. Pain is the most significant finding in patients with FSD and PBS.

Female urethral diverticulum containing a calculus: a case report.

Urethral diverticula with calculi have a low incidence as reported in the literature. This elderly female patient was first seen with recurrent urinary tract infections (UTIs), dysuria, and hematuria. She had two large stones, one in the bladder and one in a urethral diverticulum. Litholapaxy with a laser was effective in resolving both calculi. Subsequent urethral diverticulectomy was effective in removal of the urethral diverticulum.

Impact of stone location on success rates of endoscopic lithotripsy for nephrolithiasis.

OBJECTIVES: To determine whether stone location affects the stone-free rates of endoscopic lithotripsy for nephrolithiasis. METHODS: From January 2002 to August 2006, 245 patients with 272 stones, ranging from 4 to 20 mm in size, underwent ureteroscopy (URS) with laser lithotripsy at West Virginia University Hospital. The patients were followed up postoperatively with noncontrast spiral computed tomography, abdominal plain radiography, renal ultrasonography, or retrograde pyelography. Patients were considered to have been treated successfully if they had no residual stones. All pediatric patients were excluded, as were all patients with stones greater than 2 cm. Also, patients who had undergone previous shock wave lithotripsy, percutaneous nephrolithotripsy, or URS by an outside urologist were excluded. RESULTS: A total of 86 kidney stones were treated with URS and laser lithotripsy. Of these, 81 (94.2%) were successfully treated. Five patients (5.8%) had persistent stones. All 18 upper pole stones (100%) were cleared, 23 (95.8%) of 24 middle pole stones were cleared, and 40 (90.9%) of 44 lower pole stones were cleared (P = 0.338). CONCLUSIONS: URS is an important tool for treating nephroureterolithiasis with excellent success rates and minimal morbidity. The results of our study have shown that stone location does not significantly affect stone clearance rates when performing endoscopic lithotripsy for intrarenal calculi.

Encrusted cystitis managed with multimodal therapy.

Encrusted cystitis is a rare chronic inflammatory condition of the bladder. The case of a male patient with dysuria and gross hematuria accompanied by the passage of stone fragments is presented. Multimodal therapy was undertaken. He was treated with Renacidin (citric acid mixture) irrigation as an inpatient. One month later, he underwent cystourethroscopy and was determined to have residual stone and fibrosis of the prostatic urethra. The patient was then treated with cystolitholapaxy and visual internal urethrotomy. This multimodal treatment resulted in resolution of his stone burden at follow-up.

Pentosan polysulfate (Elmiron): in vitro effects on prostate cancer cells regarding cell growth and vascular endothelial growth factor production.

BACKGROUND: Elmiron (ALZA Corp, Mountain View, CA) is the only Food and Drug Administration-approved oral therapy for interstitial cystitis. We hypothesized that Elmiron would affect the growth of prostate cancer in vitro. METHODS: Prostate cancer cell lines (LnCaP, PC3, and DU145) were treated with Elmiron. Cell viability was measured by MTT (3-4, 5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide), whereas vascular endothelial growth factor (VEGF) was measured by a commercial enzyme-linked immunosorbent assay. RESULTS: Inhibition of cell growth was observed in all cell lines tested. LnCaP exhibited a mean inhibition of 12% +/- 7% at 24 hours (P = .025) and 20% +/- 15% at 72 hours (P < .001). PC3 exhibited a mean inhibition of 26% +/- 13% at 24 hours (P < .001) and 44% +/- 5% at 72 hours (P < .001). DU145 exhibited a mean inhibition of 9% +/- 6% at 24 hours (P < .015) and 30% +/- 5% at 72 hours (P < .001). PC3 cells exhibited a significant reduction in VEGF levels (P < .001). CONCLUSIONS: The reductions in cell growth and VEGF indicate that Elmiron may act as an antiangiogenic agent and may have application in the treatment of prostate cancer.

Cisplatin, gemcitabine and paclitaxel triplet chemotherapy in 50 patients with advanced or metastatic urothelial cancer.

At West Virginia University in Morgantown, we conducted a phase 2 study to investigate 50-mg/m2 cisplatin, 1,000-mg/m2 gemcitabine, and 75-mg/m2 paclitaxel (CGP) "triplet" chemotherapy for advanced urothelial cancer. Fifty patients received CGP days 1 and 8 of a 3- to 4-week cycle. Transitional cell carcinoma alone occurred in 38 patients; 12 had mixed histologic findings (adenocarcinoma or squamous cell carcinoma). Thirty-one (M0) had advanced regional disease; 19 (M1) had metastases. NCI performance status was 0 to 2 in 33 patients and 3 to 4 in 17 patients. Grade 3 or 4 toxicity occurred in 33% of patients administered 218 chemotherapy cycles. Objective tumor responses occurred in 11 M1 patients (complete in 2) and in 17 M0 patients (complete in 11). Median survival was 13.5 (M1) and 16.8 (M0) months. Our study shows that CGP for urothelial cancer is effective and has manageable toxicity. Seventy percent of our patients were ineligible for standard clinical trials.

Rhabdomyosarcoma of tunica vaginalis masquerading as hydrocele.

Paratesticular rhabdomyosarcomas are rare tumors with aggressive growth patterns. Multimodal therapy with surgery, chemotherapy, and radiotherapy provides the patient with an excellent long-term prognosis. These tumors often present in the first two decades after birth. We report on the case of an 18-year-old man with a paratesticular rhabdomyosarcoma.

Synergistic effects of Cox-1 and -2 inhibition on bladder and prostate cancer in vitro.

BACKGROUND: We hypothesized that combined treatment with cyclooxygenase (Cox)-1 (catechin) and Cox-2 (NS398)-specific inhibitors would reduce cellular proliferation synergistically in genitourinary cancer. METHODS: Bladder (T24 and TCCSUP) and prostate (DU145, LnCaP, and PC3) cancer cell lines were treated with catechin and NS398 at a dose of 100 mumol/L as single and combined treatments. Viability was measured by MTT assay at 24 and 72 hours. RESULTS: Significant synergism of Cox-1 and Cox-2 inhibitors was observed in both bladder cancer lines at both 24 and 72 hours. Synergism of Cox-1 and -2 inhibitors also was noted in the DU145 cells at 72 hours, LnCap cells at 24 hours, and PC3 at both 24 and 72 hours. CONCLUSIONS: Significant synergistic effects exhibited by the combination of Cox-1 and Cox-2 inhibitors suggest that these could become a highly effective treatment modality for carcinoma of both the bladder and prostate.

In vitro effects of pentosan polysulfate against malignant breast cells.

BACKGROUND: Pentosan polysulfate (Elmiron); (Alza Pharmaceuticals, Mountain View, CA) is the only Food and Drug Administration-approved oral therapy for interstitial cystitis (IC). Women with IC and breast cancer are often in the same age range; therefore, we hypothesize that pentosan polysulfate may also have a therapeutic effect on breast cancer cells in vitro. METHODS: Breast cancer lines MCF-7, ZR75-1, and HTB26 were treated with pentosan polysulfate at various concentrations. Cell viability was measured at 24 hours by MTT. Annexin V assay was used to determine the effect of pentosan polysulfate on apoptotic and necrotic activity. RESULTS: Pentosan polysulfate significantly inhibited the growth of the ZR75-1 cells; however, significant cellular proliferation was observed in the MCF-7 cells. A significant change in late apoptotic activity was observed with pentosan polysulfate treatment in vitro. CONCLUSIONS: Caution should be used in prescribing pentosan polysulfate for the treatment of IC in patients who are both in high-risk groups for breast cancer and premenopausal females.